tbuckley/cabot-search huggingface dataset:
Nonpharmacologic Therapies for Low Back Pain: A Systematic Review for an American College of Physicians Clinical Practice Guideline
Authors: Roger Chou, Richard Deyo, Janna Friedly, Andrea Skelly, Robin Hashimoto, Melissa Weimer, Rochelle Fu, Tracy Dana, Paul Kraegel, Jessica Griffin, Sara Grusing, Erika D. Brodt
Journal: Annals of Internal Medicine (2017)

Background: A 2007 American College of Physicians guideline addressed nonpharmacologic treatment options for low back pain. New evidence is now available. Purpose: To systematically review the current evidence on nonpharmacologic therapies for acute or chronic nonradicular or radicular low back pain. Data Sources: Ovid MEDLINE (January 2008 through February 2016), Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and reference lists. Study Selection: Randomized trials of 9 nonpharmacologic options versus sham treatment, wait list, or usual care, or of 1 nonpharmacologic option versus another. Data Extraction: One investigator abstracted data, and a second checked abstractions for accuracy; 2 investigators independently assessed study quality. Data Synthesis: The number of trials evaluating nonpharmacologic therapies ranged from 2 (tai chi) to 121 (exercise). New evidence indicates that tai chi (strength of evidence [SOE], low) and mindfulness-based stress reduction (SOE, moderate) are effective for chronic low back pain and strengthens previous findings regarding the effectiveness of yoga (SOE, moderate). Evidence continues to support the effectiveness of exercise, psychological therapies, multidisciplinary rehabilitation, spinal manipulation, massage, and acupuncture for chronic low back pain (SOE, low to moderate). Limited evidence shows that acupuncture is modestly effective for acute low back pain (SOE, low). The magnitude of pain benefits was small to moderate and generally short term; effects on function generally were smaller than effects on pain. Limitation: Qualitatively synthesized new trials with prior meta-analyses, restricted to English-language studies; heterogeneity in treatment techniques; and inability to exclude placebo effects. Conclusion: Several nonpharmacologic therapies for primarily chronic low back pain are associated with small to moderate, usually short-term effects on pain; findings include new evidence on mind–body interventions. Primary Funding Source: Agency for Healthcare Research and Quality. (PROSPERO: CRD42014014735)
I-OPen: inferior outcomes of penta-refractory compared to penta-exposed multiple myeloma patients
Authors: Sarvarinder K. Gill, Rashmi Unawane, Shuqi Wang, Jaeil Ahn, Adolfo Aleman, David S. Siegel, David H. Vesole, Harsh Parmar, Pooja Phull, Noa Biran
Journal: Blood Cancer Journal (2022)
One-Year Mental and Physical Health Assessment in Survivors after Extracorporeal Membrane Oxygenation for COVID-19–related Acute Respiratory Distress Syndrome
Authors: Juliette Chommeloux, Simon Valentin, Hadrien Winiszewski, Mélanie Adda, Marc Pineton de Chambrun, Quentin Moyon, Alexis Mathian, Gilles Capellier, Christophe Guervilly, Bruno Levy, Pierre Jaquet, Romain Sonneville, Guillaume Voiriot, Alexandre Demoule, Samia Boussouar, Benoit Painvin, Guillaume Lebreton, Alain Combes, Matthieu Schmidt
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

Rationale: Long-term outcomes of patients with coronavirus disease (COVID-19)-related acute respiratory distress syndrome treated with extracorporeal membrane oxygenation (ECMO) are unknown. Objectives: To assess physical examination, pulmonary function tests, anxiety, depression, post-traumatic stress disorder and quality of life at 6 and 12 months after ECMO onset. Methods: Multicenter, prospective study in patients who received ECMO for COVID-19 acute respiratory distress syndrome from March to June 2020 and survived hospital discharge. Measurements and Main Results: Of 80 eligible patients, 62 were enrolled in seven French ICUs. ECMO and invasive mechanical ventilation duration were 18 (11-25) and 36 (27-62) days, respectively. All were alive, but only 19/50 (38%) returned to work and 13/42 (31%) had recovered a normal sex drive at 1 year. Pulmonary function tests were almost normal at 6 months, except for DlCO, which was still impaired at 12 months. Mental health, role-emotional, and role-physical were the most impaired domain compared with patients receiving ECMO who did not have COVID-19. One year after ICU admission, 19/43 (44%) patients had significant anxiety, 18/43 (42%) had depression symptoms, and 21/50 (42%) were at risk for post-traumatic stress disorders. Conclusions: Despite the partial recovery of the lung function tests at 1 year, the physical and psychological function of this population remains impaired. Based on the comparison with long-term follow-up of patients receiving ECMO who did not have COVID-19, poor mental and physical health may be more related to COVID-19 than to ECMO in itself, although this needs confirmation.
Pathogenesis of Zika Virus Infection
Authors: Maria I. Giraldo, Maria Gonzalez-Orozco, Ricardo Rajsbaum
Journal: Annual Review of Pathology Mechanisms of Disease (2022)

Zika virus (ZIKV) is an emerging virus from the Flaviviridae family that is transmitted to humans by mosquito vectors and represents an important health problem. Infections in pregnant women are of major concern because of potential devastating consequences during pregnancy and have been associated with microcephaly in newborns. ZIKV has a unique ability to use the host machinery to promote viral replication in a tissue-specific manner, resulting in characteristic pathological disorders. Recent studies have proposed that the host ubiquitin system acts as a major determinant of ZIKV tropism by providing the virus with an enhanced ability to enter new cells. In addition, ZIKV has developed mechanisms to evade the host immune response, thereby allowing the establishment of viral persistence and enhancing viral pathogenesis. We discuss recent reports on the mechanisms used by ZIKV to replicate efficiently, and we highlight potential new areas of research for the development of therapeutic approaches.
Hybrid immunity in immunocompromised patients with CLL after SARS-CoV-2 infection followed by booster mRNA vaccination
Authors: Lisa Blixt, Yu Gao, David Wullimann, Hanna Murén Ingelman-Sundberg, Sandra Muschiol, Katie Healy, Gordana Bogdanovic, Elisa Pin, Peter Nilsson, Christian Kjellander, Alba Grifoni, Alessandro Sette, Margaret Sällberg Chen, Hans-Gustaf Ljunggren, Marcus Buggert, Lotta Hansson, Anders Österborg
Journal: Blood (2022)

Patients with chronic lymphocytic leukemia (CLL) are immunocompromised. 1 They are at high risk for developing severe COVID-19 [2][3][4] and mount suboptimal immunity after messenger RNA (mRNA) vaccination, 5,6 but they have slightly conflicting results regarding cellular immunity. 7,8In a "hybrid immunity" setting, immune protection is influenced by prior infection status and vaccination.Here, we studied humoral and cellular hybrid immunity in a CLL cohort of 29 patients with a history of COVID-19 2 and 3 consecutive mRNA vaccinations against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (2 patients received 2 doses).The study was approved by Swedish Ethical Review Authority (www.etikprovningsmyndigheten.se).Written informed consent was obtained before sampling.Serum and saliva antibodies were measured prevaccination, after dose 2, and before and after dose 3 vaccinations.SARS-CoV-2 immunoglobulin G (IgG) antibodies in serum were analyzed using Roche Elecsys qualitative anti-SARS-CoV-2 and quantitative anti-SARS-CoV-2 immunoassays as described elsewhere. 2,5Saliva was collected using a self-sampling technique, and SARS-CoV-2 IgG antibodies were analyzed as described elsewhere. 9-11T-cell responses were analyzed by activation-induced marker assay as described elsewhere 12 before vaccination and before and after dose 3. We also applied the interferon gamma (IFN-γ) ELISpot as described elsewhere. 2,7Experimental methods are described in the supplemental Methods, available on the Blood website.
Patients and healthcare professionals in priority setting partnerships: two very different sides of the same coin
Authors: Adewale Adebajo
Journal: BMJ (2022)

professorassociate medical director and consultant rheumatologist 1It is easily forgotten that healthcare professionals are frequently patients themselves, but potentially with very different power dynamics.I recently had cause to reflect on this issue, due to my involvement in two separate James Lind Alliance priority setting partnerships. 1The purpose and methodology of these partnerships are well established and well documented.In brief, the JLA methodology involves setting up a steering group to oversee the project and inviting patients, carers, and clinicians to participate in the project, gathering treatment and intervention uncertainties from surveys and from the literature and then ranking these uncertainties into a top 10, through discussion and voting by patients, carers and clinicians as equal partners.
Resolution Pharmacology: Focus on Pro-Resolving Annexin A1 and Lipid Mediators for Therapeutic Innovation in Inflammation
Authors: Mauro Perretti, Jesmond Dalli
Journal: The Annual Review of Pharmacology and Toxicology (2022)

Chronic diseases that affect our society are made more complex by comorbidities and are poorly managed by the current pharmacology. While all present inflammatory etiopathogeneses, there is an unmet need for better clinical management of these diseases and their multiple symptoms. We discuss here an innovative approach based on the biology of the resolution of inflammation. Studying endogenous pro-resolving peptide and lipid mediators, how they are formed, and which target they interact with, can offer innovative options through augmenting the expression or function of pro-resolving pathways or mimicking their actions with novel targeted molecules. In all cases, resolution offers innovation for the treatment of the primary cause of a given disease and/or for the management of its comorbidities, ultimately improving patient quality of life. By implementing resolution pharmacology, we harness the whole physiology of inflammation, with the potential to bring a marked change in the management of inflammatory conditions.
Zebrafish as a Mainstream Model for In Vivo Systems Pharmacology and Toxicology
Authors: Calum A. MacRae, Randall T. Peterson
Journal: The Annual Review of Pharmacology and Toxicology (2022)

Pharmacology and toxicology are part of a much broader effort to understand the relationship between chemistry and biology. While biomedicine has necessarily focused on specific cases, typically of direct human relevance, there are real advantages in pursuing more systematic approaches to characterizing how health and disease are influenced by small molecules and other interventions. In this context, the zebrafish is now established as the representative screenable vertebrate and, through ongoing advances in the available scale of genome editing and automated phenotyping, is beginning to address systems-level solutions to some biomedical problems. The addition of broader efforts to integrate information content across preclinical model organisms and the incorporation of rigorous analytics, including closed-loop deep learning, will facilitate efforts to create systems pharmacology and toxicology with the ability to continuously optimize chemical biological interactions around societal needs. In this review, we outline progress toward this goal.
Cost-effectiveness of pharmacy-led versus conventionally delivered antiviral treatment for hepatitis C in patients receiving opioid substitution therapy: An economic evaluation alongside a pragmatic cluster randomised trial
Authors: G. Myring, A.G. Lim, W. Hollingworth, H. McLeod, L. Beer, P. Vickerman, M. Hickman, A. Radley, J.F. Dillon
Journal: Journal of Infection (2022)
Costunolide covalently targets NACHT domain of NLRP3 to inhibit inflammasome activation and alleviate NLRP3-driven inflammatory diseases
Authors: Haowen Xu, Jiahao Chen, Pan Chen, Weifeng Li, Jingjing Shao, Shanshan Hong, Yi Wang, Lingfeng Chen, Wu Luo, Guang Liang
Journal: Acta Pharmaceutica Sinica B (2022)

The NLRP3 inflammasome's core and most specific protein, NLRP3, has a variety of functions in inflammation-driven diseases. Costunolide (COS) is the major active ingredient of the traditional Chinese medicinal herb Saussurea lappa and has anti-inflammatory activity, but the principal mechanism and molecular target of COS remain unclear. Here, we show that COS covalently binds to cysteine 598 in NACHT domain of NLRP3, altering the ATPase activity and assembly of NLRP3 inflammasome. We declare COS's great anti-inflammasome efficacy in macrophages and disease models of gouty arthritis and ulcerative colitis via inhibiting NLRP3 inflammasome activation. We also reveal that the α-methylene-γ-butyrolactone motif in sesquiterpene lactone is the certain active group in inhibiting NLRP3 activation. Taken together, NLRP3 is identified as a direct target of COS for its anti-inflammasome activity. COS, especially the α-methylene-γ-butyrolactone motif in COS structure, might be used to design and produce novel NLRP3 inhibitors as a lead compound.
Bispecific sigma-1 receptor antagonism and mu-opioid receptor partial agonism: WLB-73502, an analgesic with improved efficacy and safety profile compared to strong opioids
Authors: Alba Vidal-Torres, Begoña Fernández-Pastor, Mónica García, Eva Ayet, Anna Cabot, Javier Burgueño, Xavier Monroy, Bertrand Aubel, Xavier Codony, Luz Romero, Rosalía Pascual, Maria Teresa Serafini, Gregorio Encina, Carmen Almansa, Daniel Zamanillo, Manuel Merlos, José Miguel Vela
Journal: Acta Pharmaceutica Sinica B (2022)

Opioids are the most effective painkillers, but their benefit-risk balance often hinder their therapeutic use. WLB-73502 is a dual, bispecific compound that binds sigma-1 (S1R) and mu-opioid (MOR) receptors. WLB-73502 is an antagonist at the S1R. It behaved as a partial MOR agonist at the G-protein pathway and produced no/unsignificant β-arrestin-2 recruitment, thus demonstrating low intrinsic efficacy on MOR at both signalling pathways. Despite its partial MOR agonism, WLB-73502 exerted full antinociceptive efficacy, with potency superior to morphine and similar to oxycodone against nociceptive, inflammatory and osteoarthritis pain, and superior to both morphine and oxycodone against neuropathic pain. WLB-73502 crosses the blood-brain barrier and binds brain S1R and MOR to an extent consistent with its antinociceptive effect. Contrary to morphine and oxycodone, tolerance to its antinociceptive effect did not develop after repeated 4-week administration. Also, contrary to opioid comparators, WLB-73502 did not inhibit gastrointestinal transit or respiratory function in rats at doses inducing full efficacy, and it was devoid of proemetic effect (retching and vomiting) in ferrets at potentially effective doses. WLB-73502 benefits from its bivalent S1R antagonist and partial MOR agonist nature to provide an improved antinociceptive and safety profile respect to strong opioid therapy.
Salmonella-mediated blood‒brain barrier penetration, tumor homing and tumor microenvironment regulation for enhanced chemo/bacterial glioma therapy
Authors: Ze Mi, Qing Yao, Yan Qi, Jinhai Zheng, Jiahao Liu, Zhenguo Liu, Hongpei Tan, Xiaoqian Ma, Wenhu Zhou, Pengfei Rong
Journal: Acta Pharmaceutica Sinica B (2022)

Chemotherapy is an important adjuvant treatment of glioma, while the efficacy is far from satisfactory, due not only to the biological barriers of blood‒brain barrier (BBB) and blood‒tumor barrier (BTB) but also to the intrinsic resistance of glioma cells via multiple survival mechanisms such as up-regulation of P-glycoprotein (P-gp). To address these limitations, we report a bacteria-based drug delivery strategy for BBB/BTB transportation, glioma targeting, and chemo-sensitization. Bacteria selectively colonized into hypoxic tumor region and modulated tumor microenvironment, including macrophages repolarization and neutrophils infiltration. Specifically, tumor migration of neutrophils was employed as hitchhiking delivery of doxorubicin (DOX)-loaded bacterial outer membrane vesicles (OMVs/DOX). By virtue of the surface pathogen-associated molecular patterns derived from native bacteria, OMVs/DOX could be selectively recognized by neutrophils, thus facilitating glioma targeted delivery of drug with significantly enhanced tumor accumulation by 18-fold as compared to the classical passive targeting effect. Moreover, the P-gp expression on tumor cells was silenced by bacteria type III secretion effector to sensitize the efficacy of DOX, resulting in complete tumor eradication with 100% survival of all treated mice. In addition, the colonized bacteria were finally cleared by anti-bacterial activity of DOX to minimize the potential infection risk, and cardiotoxicity of DOX was also avoided, achieving excellent compatibility. This work provides an efficient trans-BBB/BTB drug delivery strategy via cell hitchhiking for enhanced glioma therapy.
NIR‐Assisted MgO‐Based Polydopamine Nanoparticles for Targeted Treatment of Parkinson's Disease through the Blood–Brain Barrier
Authors: Yifei Gao, Yuxue Cheng, Jiapeng Chen, Danmin Lin, Chao Liu, Ling‐Kun Zhang, Liang Yin, Runcai Yang, Yan‐Qing Guan
Journal: Advanced Healthcare Materials (2022)

The blood-brain barrier (BBB) is a major limiting factor that prevents the treatment of Parkinson's disease (PD). In the present study, MgOp@PPLP nanoparticles are explored by using MgO nanoparticles as a substrate, polydopamine as a shell, wrapping anti-SNCA plasmid inside, and modifying polyethylene glycol, lactoferrin, and puerarin on the surface to improve the hydrophilicity, brain targeting and antioxidant properties of the particles, respectively. MgOp@PPLP exhibits superior near-infrared radiation (NIR) response. Under the guidance of photothermal effect, these MgOp@PPLP particles are capable of penetrating the BBB and be taken up by neuronal cells to exert gene therapy and antioxidant therapy. In both in vivo and in vitro models of PD, MgOp@PPLP exhibits good neuroprotective effects. Therefore, combined with noninvasive NIR radiation, MgOp@PPLP nanoplatform with good biocompatibility becomes an ideal material to combat neurodegenerative diseases.
Pharmacokinetics of Intramuscularly Administered Thermoresponsive Polymers
Authors: Ondřej Groborz, Kristýna Kolouchová, Jan Pankrác, Peter Keša, Jan Kadlec, Tereza Krunclová, Aneta Pierzynová, Jaromír Šrámek, Mária Hovořáková, Linda Dalecká, Zuzana Pavlíková, Petr Matouš, Petr Páral, Lenka Loukotová, Pavel Švec, Hynek Beneš, Lubomír Štěpánek, David Dunlop, Carlos V. Melo, Luděk Šefc, Tomáš Slanina, Jiří Beneš, Sandra Van Vlierberghe, Richard Hoogenboom, Martin Hrubý
Journal: Advanced Healthcare Materials (2022)

Aqueous solutions of some polymers exhibit a lower critical solution temperature (LCST); that is, they form phase-separated aggregates when heated above a threshold temperature. Such polymers found many promising (bio)medical applications, including in situ thermogelling with controlled drug release, polymer-supported radiotherapy (brachytherapy), immunotherapy, and wound dressing, among others. Yet, despite the extensive research on medicinal applications of thermoresponsive polymers, their biodistribution and fate after administration remained unknown. Thus, herein, they studied the pharmacokinetics of four different thermoresponsive polyacrylamides after intramuscular administration in mice. In vivo, these thermoresponsive polymers formed depots that subsequently dissolved with a two-phase kinetics (depot maturation, slow redissolution) with half-lives 2 weeks to 5 months, as depot vitrification prolonged their half-lives. Additionally, the decrease of T
Long‐term outcomes and predictors of early response, late relapse, and survival for patients treated with bispecific <scp>LV20</scp>.19 <scp>CAR</scp> T‐cells
Authors: Joanna C. Zurko, Timothy S. Fenske, Bryon D. Johnson, Daniel Bucklan, Aniko Szabo, Huiqing Xu, Katherine Chaney, Mehdi Hamadani, Parameswaran Hari, Nirav N. Shah
Journal: American Journal of Hematology (2022)

We previously reported results of a first-in-human trial of bispecific LV20.19 chimeric antigen receptor T-cell (CAR-T) therapy, demonstrating high response rates in patients with relapsed, refractory (R/R) B-cell malignancies. We now report two-year survival outcomes and predictors of early response, late relapse, and survival. Patients from the previously reported phase 1 dose escalation and expansion trial of LV20.19 CAR-T therapy (NCT03019055) treated at target dose of 2.5 × 106 cells/kg (n = 16) were included in this updated analysis. Two-year progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan-Meier method. The relationship of in-vivo CAR-T expansion, tumor burden, and effector: target ratio on early response (day 28) and late relapse (>180 days post-CAR-T) were assessed. Exact log-rank testing was performed to evaluate the impacts of clinical variables on survival outcomes. With a median of 31 months (range 27-40) of follow-up, two-year PFS and OS were 44% and 69%. Median PFS and OS were 15.6 months and not reached, respectively. For CAR-naïve large B-cell lymphoma patients (n = 8), two-year PFS and OS were 50% and 75%. No patient with progression experienced dual target antigen (CD19 or CD20) loss on post-relapse biopsy. Lower in vivo expansion was strongly associated with late relapse. Early treatment response was impeded by high metabolic tumor volume and low effector: target ratio. Bridging therapy and higher absolute lymphocyte count on day of CAR-T infusion were associated with inferior survival outcomes. In conclusion, this initial trial of LV20.19 CAR-T demonstrates a signal for favorable long-term outcomes for patients with R/R B-cell malignancies.
An enzyme-responsive and transformable PD-L1 blocking peptide-photosensitizer conjugate enables efficient photothermal immunotherapy for breast cancer
Authors: Yanan Sun, Bochen Lyu, Chang Yang, Bing He, Hua Zhang, Xueqing Wang, Qiang Zhang, Wenbing Dai
Journal: Bioactive Materials (2022)

Mild photothermal therapy combined with immune checkpoint blockade has received increasing attention for the treatment of advanced or metastatic cancers due to its good therapeutic efficacy. However, it remains a challenge to facilely integrate the two therapies and make it potential for clinical translation. This work designed a peptide-photosensitizer conjugate (PPC), which consisted of a PD-L1 antagonist peptide (CVRARTR), an MMP-2 specific cleavable sequence, a self-assembling motif, and the photosensitizer Purpurin 18. The single-component PPC can self-assemble into nanospheres which is suitable for intravenous injection. The PPC nanosphere is cleaved by MMP-2 when it accumulates in tumor sites, thereby initiating the cancer-specific release of the antagonist peptide. Simultaneously, the nanospheres gradually transform into co-assembled nanofibers, which promotes the retention of the remaining parts within the tumor. In vivo studies demonstrated that PPC nanospheres under laser irradiation promote the infiltration of cytotoxic T lymphocytes and maturation of DCs, which sensitize 4T1 tumor cells to immune checkpoint blockade therapy. Therefore, PPC nanospheres inhibit tumor growth efficiently both in situ and distally and blocked the formation of lung metastases. The present study provides a simple and efficient integrated strategy for breast cancer photoimmunotherapy.